Risks of Myocardial Infarction and Mortality in Patients with Incident Rheumatoid Arthritis Compared with a Matched General Population: A Danish Nationwide Cohort Study

Brian Bridal Løgstrup,1 Torkell Ellingsen,2 Alma B Pedersen,3 Helene Matilde Lundsgaard Svane,3 Kevin KW Olesen,1 Christine Gyldenkerne,1 Ellen-Margrethe Hauge,4 Henrik Toft Sørensen,3 Hans Erik Bøtker,5 Michael Maeng1 1Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark; 2Department of Rheumatology, University of Southern Denmark, Odense, Denmark; 3Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark; 4Department of Rheumatology, Aarhus University Hospital, Aarhus, Denmark; 5Instutute of Clinical Medicine, Health, Aarhus University, Aarhus, DenmarkCorrespondence: Brian Bridal Løgstrup, Department of Cardiology, Aarhus University Hospital, Palle Juul Jensens Boulevard 99, Aarhus, 8200 Aarhus N, Denmark, Email bbl@skejby.rm.dkBackground and Aims: Rheumatoid arthritis (RA) is increasingly being recognized as cardiovascular risk factor. We examined temporal trends in the risks of myocardial infarction (MI) and all-cause mortality in patients with newly diagnosed RA without a history of cardiovascular disease (CVD) compared with a matched general population.Methods and Results: Patients with a first diagnosis of RA without prior CVD (N=20,937) were identified through national health registries between 1996 and 2017. On the index date, each patient was matched by age and sex to five individuals from the general population with neither RA nor CVD (N=104,685) and followed for 5 years. Among patients with RA, the 5-year cumulative incidence proportions for MI declined from 2.6% in 1996– 2000 to 1.5% in 2011– 2017 (hazard ratio (HR) 0.59; 95% CI 0.45– 0.78), whereas all-cause mortality decreased from 9.3% to 7.7% (HR 0.83; 95% CI 0.72– 0.95). The reduced risk of MI in patients with RA mirrored the decline observed in a matched general population while the mortality gap between RA and general population individuals was reduced between 1996 and 2010. Statin prescription fillings at 1-year follow-up, a proxy for prophylactic medical intervention, was highest in 2011– 2017, reaching 19% among RA patients as well as general population individuals.Conclusion: Despite a gradual decline in the risk of MI and all-cause mortality from 1996 to 2017, patients with RA remain at higher risk of both MI and death than their matched general population individuals. This increased risk was not reflected by improved primary prophylactic medical interventions.Plain Language Summary: What is already known about this subject?Rheumatoid arthritis (RA) is a cardiovascular risk factor and is associated with an approximately 50% higher relative risk of major adverse cardiovascular events compared with the general population.Why was the study conducted?We aimed to examine how cardiovascular risks and outcomes in people with newly diagnosed RA have changed over time and to identify opportunities to improve prevention and care.What does this study add?This Danish nationwide study of patients with newly diagnosed RA shows substantial improvement in outcomes over two decades. From 1996-2000 to 2011-2017, the 5-year risk of myocardial infarction fell by 41%, and the 5-year risk of all-cause mortality fell by 17%.The decline in risk of myocardial infarction paralleled the decline in the general population, so the excess risk of myocardial infarction associated with RA persisted at about 50% across the full study period.All-cause mortality, however, improved only among patients with RA and remained unchanged in the general population. Despite this improvement, RA still carried a 13% higher relative risk of all-cause mortality in 2011-2017.Use of preventive cardiovascular disease medications increased steadily in both groups; in the most recent period, 19% of patients with RA received statins within one year after diagnosis.How might this impact clinical practice or future developments?Clinicians should inform patients with RA about their increased cardiovascular risk and support appropriate risk-reduction strategies.These findings underscore the need to clearer guidance on cardiovascular prevention at the time of RA diagnosis. Keywords: rheumatoid arthritis, cardiovascular disease, coronary heart disease, acute myocardial infarction, mortality, outcome, statins, medical treatment, cohort study